methyl 11β,17α,20β-trihydroxy-9α-fluoro-3-oxo-1,4-pregnadiene-21-oate | 428510-22-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: methyl 11β,17α,20β-trihydroxy-9α-fluoro-3-oxo-1,4-pregnadiene-21-oate
• 英文别名: methyl 11β,17α,20β-trihydroxy-9α-fluoro-3-oxo-1,4-pregnadien-21-oate；methyl (2S)-2-[(8S,9R,10S,11S,13S,14S,17R)-9-fluoro-11,17-dihydroxy-10,13-dimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl]-2-hydroxyacetate
• CAS: 428510-22-9
• 化学式: C₂₂H₂₉FO₆
• 分子量: 408.467
• InChiKey: QOLAYHKSFFJKQQ-NOLGVZBPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2,2-二甲氧基丙烷 、 methyl 11β,17α,20β-trihydroxy-9α-fluoro-3-oxo-1,4-pregnadiene-21-oate 在 对甲苯磺酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 methyl 11β,17α,20β-trihydroxy-9α-fluoro-3-oxo-1,4-pregnadiene-21-oate 17,20-acetonide
  参考文献：
  名称：

  Effect of chirality at C-20 of methyl 11β,17α,20-trihydroxy-3-oxo-1,4-pregnadien-21-oate derivatives on antiinflammatory activity

  摘要：

  In an effort to determine the C-20 chirality effect on the antiinflammatory activity of 17beta-glycolate esters, methyl 11beta,17alpha,20-trihydroxy-3-oxo-1,4-pregnadien-21-oate and its 9alpha-fluoro analog, their acetonide and their carbonate derivatives were synthesized and evaluated. The agents were tested for their binding potency to the macrophage glucocorticoid receptor, and their effect on LPS-induced nitric oxide generation in RAW 264.7 cells. The acetonide derivatives showed the highest binding affinity while the triols and carbonates bound rather poorly to the receptors. With the exception of the triols, the a-isomer in each pair of the agents exhibited higher binding affinity to the receptor than its corresponding beta-isomer, clearly indicating that C-20 chirality has a significant effect on anti inflammatory activity. In addition, the alpha-isomers of the acetonides showed substantially higher binding affinity than the parent compound, prednisolone. In contrast to the high binding activity exhibited by some of the acetonides, all of the agents showed weak inhibitory effect on NO generation. Metabolic inactivation during assessment of NO inhibition may play it role in the divergence noted between receptor affinity and the measured biologic activity resulting from the binding. (C) 2002 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(01)00189-1
• 作为产物：
  描述：

  异氟泼尼松 在 copper diacetate 作用下， 以 甲醇 、 乙醚 、 乙酸乙酯 为溶剂， 反应 49.0h， 生成 methyl 11β,17α,20β-trihydroxy-9α-fluoro-3-oxo-1,4-pregnadiene-21-oate
  参考文献：
  名称：

  Effect of chirality at C-20 of methyl 11β,17α,20-trihydroxy-3-oxo-1,4-pregnadien-21-oate derivatives on antiinflammatory activity

  摘要：

  In an effort to determine the C-20 chirality effect on the antiinflammatory activity of 17beta-glycolate esters, methyl 11beta,17alpha,20-trihydroxy-3-oxo-1,4-pregnadien-21-oate and its 9alpha-fluoro analog, their acetonide and their carbonate derivatives were synthesized and evaluated. The agents were tested for their binding potency to the macrophage glucocorticoid receptor, and their effect on LPS-induced nitric oxide generation in RAW 264.7 cells. The acetonide derivatives showed the highest binding affinity while the triols and carbonates bound rather poorly to the receptors. With the exception of the triols, the a-isomer in each pair of the agents exhibited higher binding affinity to the receptor than its corresponding beta-isomer, clearly indicating that C-20 chirality has a significant effect on anti inflammatory activity. In addition, the alpha-isomers of the acetonides showed substantially higher binding affinity than the parent compound, prednisolone. In contrast to the high binding activity exhibited by some of the acetonides, all of the agents showed weak inhibitory effect on NO generation. Metabolic inactivation during assessment of NO inhibition may play it role in the divergence noted between receptor affinity and the measured biologic activity resulting from the binding. (C) 2002 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(01)00189-1